Poxviruses are large double-stranded DNA viruses with genomes that range from 130 to 379 kbp. Poxviruses have worldwide distribution and infect a wide variety of animals, including insects, birds and mammals. Since the eradication of smallpox and the cessation of vaccination programs, various poxvirus infections have begun to re-emerge clinically worldwide. Variola virus continues to present a bioterrorism threat and several other poxviruses infect humans, causing morbidity and mortality: molluscum contagiosum virus (MCV), monkeypox virus, Tanapox virus, Yaba-like disease virus, cowpox virus and Cantagalo virus (evolved from a vaccinia virus (VV) vaccine strain). The prevalence of poxviruses in animals and humans and their propensity for recombination and gene acquisition suggest that it would be unwise to discount them as important human pathogens. This is especially true, since most emerging infectious diseases are zoonoses, crossing from animals to humans, and poxviruses are known to acquire mutations and become highly pathogenic in a new animal species.
The A35R gene is highly conserved in mammalian-tropic poxviruses. VV is the model poxvirus to study the A35R protein (called A35R in Copenhagen strain, 0158 in WR strain and a number of other designations in all mammalian-tropic poxviruses) and its role in the virus life cycle. The present invention provides the discovery that the A35R protein has immunoregulatory activity. Thus, the present invention overcomes previous shortcomings in the art by providing an A35R protein and biologically active fragments thereof, as well as nucleic acids encoding this protein and its fragments and antibodies and inhibitors specific thereto. These compositions are used, for example, in methods of diagnosing, treating and preventing infection by poxvirus, treating and preventing other disorders and in modulating immune responses.